Method and Apparatus for Providing Data Processing and Control in a Medical Communication System

ABSTRACT

Methods and apparatus for providing data processing and control for use in a medical communication system are provided.

RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 14/223,893 filed Mar. 24, 2014, now U.S. Pat. No. 9,804,150,which is a continuation of U.S. patent application Ser. No. 13/567,038filed Aug. 4, 2012, now U.S. Pat. No. 8,682,615, which is a continuationof U.S. patent application Ser. No. 12/152,652 filed May 14, 2008, nowU.S. Pat. No. 8,239,166, entitled “Method And Apparatus For ProvidingData Processing And Control In A Medical Communication System”, whichclaims priority under 35 U.S.C. §119(e) to U.S. provisional applicationno. 60/917,837 filed May 14, 2007, entitled “Method And Apparatus ForProviding Data Processing And Control In A Medical CommunicationSystem”, the disclosures of each of which are incorporated herein byreference for all purposes.

BACKGROUND

Analyte, e.g., glucose monitoring systems including continuous anddiscrete monitoring systems generally include a small, lightweightbattery powered and microprocessor controlled system which is configuredto detect signals proportional to the corresponding measured glucoselevels using an electrometer, and RF signals to transmit the collecteddata. One aspect of certain analyte monitoring systems include atranscutaneous or subcutaneous analyte sensor configuration which is,for example, partially mounted on the skin of a subject whose analytelevel is to be monitored. The sensor cell may use a two orthree-electrode (work, reference and counter electrodes) configurationdriven by a controlled potential (potentiostat) analog circuit connectedthrough a contact system.

The analyte sensor may be configured so that a portion thereof is placedunder the skin of the patient so as to detect the analyte levels of thepatient, and another portion or segment of the analyte sensor that is incommunication with the transmitter unit. The transmitter unit isconfigured to transmit the analyte levels detected by the sensor over awireless communication link such as an RF (radio frequency)communication link to a receiver/monitor unit. The receiver/monitor unitperforms data analysis, among others on the received analyte levels togenerate information pertaining to the monitored analyte levels. Toprovide flexibility in analyte sensor manufacturing and/or design, amongothers, tolerance of a larger range of the analyte sensor sensitivitiesfor processing by the transmitter unit is desirable.

In view of the foregoing, it would be desirable to have a method andsystem for providing data processing and control for use in medicaltelemetry systems such as, for example, analyte monitoring systems.

SUMMARY

In one embodiment, method and apparatus for sampling a predeterminednumber of in vivo analyte sensors, determining a sensitivity value foreach of the sampled predetermined number of analyte sensors, anddetermining a mean sensitivity based on the sensitivity value of thepredetermined number of analyte sensors, is disclosed.

These and other objects, features and advantages of the presentdisclosure will become more fully apparent from the following detaileddescription of the embodiments, the appended claims and the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a block diagram of a data monitoring and managementsystem for practicing one or more embodiments of the present disclosure;

FIG. 2 is a block diagram of the transmitter unit of the data monitoringand management system shown in FIG. 1 in accordance with one embodimentof the present disclosure;

FIG. 3 is a block diagram of the receiver/monitor unit of the datamonitoring and management system shown in FIG. 1 in accordance with oneembodiment of the present disclosure;

FIGS. 4A-4B illustrate a perspective view and a cross sectional view,respectively of an analyte sensor in accordance with one embodiment ofthe present disclosure;

FIG. 5 is a flowchart illustrating ambient temperature compensationroutine for determining on-skin temperature information in accordancewith one embodiment of the present disclosure;

FIG. 6 is a flowchart illustrating digital anti-aliasing filteringrouting in accordance with one embodiment of the present disclosure;

FIG. 7 is a flowchart illustrating actual or potential sensor insertionor removal detection routine in accordance with one embodiment of thepresent disclosure;

FIG. 8 is a flowchart illustrating receiver unit processingcorresponding to the actual or potential sensor insertion or removaldetection routine of FIG. 7 in accordance with one embodiment of thepresent disclosure;

FIG. 9 is a flowchart illustrating data processing corresponding to theactual or potential sensor insertion or removal detection routine inaccordance with another embodiment of the present disclosure;

FIG. 10 is a flowchart illustrating a concurrent passive notificationroutine in the data receiver/monitor unit of the data monitoring andmanagement system of FIG. 1 in accordance with one embodiment of thepresent disclosure;

FIG. 11 is a flowchart illustrating a data quality verification routinein accordance with one embodiment of the present disclosure;

FIG. 12 is a flowchart illustrating a rate variance filtering routine inaccordance with one embodiment of the present disclosure;

FIG. 13 is a flowchart illustrating a composite sensor sensitivitydetermination routine in accordance with one embodiment of the presentdisclosure;

FIG. 14 is a flowchart illustrating an outlier data point verificationroutine in accordance with one embodiment of the present disclosure;

FIG. 15 is a flowchart illustrating a sensor stability verificationroutine in accordance with one embodiment of the present disclosure;

FIG. 16 illustrates analyte sensor code determination in accordance withone embodiment of the present disclosure;

FIG. 17 illustrates an early user notification function associated withthe analyte sensor condition in one aspect of the present disclosure;

FIG. 18 illustrates uncertainty estimation associated with glucose levelrate of change determination in one aspect of the present disclosure;

FIG. 19 illustrates glucose trend determination in accordance with oneembodiment of the present disclosure; and

FIG. 20 illustrates glucose trend determination in accordance withanother embodiment of the present disclosure.

DETAILED DESCRIPTION

As described in further detail below, in accordance with the variousembodiments of the present disclosure, there is provided a method andapparatus for providing data processing and control for use in a medicaltelemetry system. In particular, within the scope of the presentdisclosure, there are provided method and system for providing datacommunication and control for use in a medical telemetry system such as,for example, a continuous glucose monitoring system.

FIG. 1 illustrates a data monitoring and management system such as, forexample, analyte (e.g., glucose) monitoring system 100 in accordancewith one embodiment of the present disclosure. The subject invention isfurther described primarily with respect to a glucose monitoring systemfor convenience and such description is in no way intended to limit thescope of the invention. It is to be understood that the analytemonitoring system may be configured to monitor a variety of analytes,e.g., lactate, and the like.

Analytes that may be monitored include, for example, acetyl choline,amylase, bilirubin, cholesterol, chorionic gonadotropin, creatine kinase(e.g., CK-MB), creatine, DNA, fructosamine, glucose, glutamine, growthhormones, hormones, ketones, lactate, peroxide, prostate-specificantigen, prothrombin, RNA, thyroid stimulating hormone, and troponin.The concentration of drugs, such as, for example, antibiotics (e.g.,gentamicin, vancomycin, and the like), digitoxin, digoxin, drugs ofabuse, theophylline, and warfarin, may also be monitored.

The analyte monitoring system 100 includes a sensor 101, a transmitterunit 102 coupled to the sensor 101, and a primary receiver unit 104which is configured to communicate with the transmitter unit 102 via acommunication link 103. The primary receiver unit 104 may be furtherconfigured to transmit data to a data processing terminal 105 forevaluating the data received by the primary receiver unit 104. Moreover,the data processing terminal in one embodiment may be configured toreceive data directly from the transmitter unit 102 via a communicationlink which may optionally be configured for bi-directionalcommunication.

Also shown in FIG. 1 is a secondary receiver unit 106 which isoperatively coupled to the communication link 103 and configured toreceive data transmitted from the transmitter unit 102. Moreover, asshown in the Figure, the secondary receiver unit 106 is configured tocommunicate with the primary receiver unit 104 as well as the dataprocessing terminal 105. Indeed, the secondary receiver unit 106 may beconfigured for bi-directional wireless communication with each of theprimary receiver unit 104 and the data processing terminal 105. Asdiscussed in further detail below, in one embodiment of the presentdisclosure, the secondary receiver unit 106 may be configured to includea limited number of functions and features as compared with the primaryreceiver unit 104. As such, the secondary receiver unit 106 may beconfigured substantially in a smaller compact housing or embodied in adevice such as a wrist watch, for example. Alternatively, the secondaryreceiver unit 106 may be configured with the same or substantiallysimilar functionality as the primary receiver unit 104, and may beconfigured to be used in conjunction with a docking cradle unit forplacement by bedside, for night time monitoring, and/or bi-directionalcommunication device.

Only one sensor 101, transmitter unit 102, communication link 103, anddata processing terminal 105 are shown in the embodiment of the analytemonitoring system 100 illustrated in FIG. 1. However, it will beappreciated by one of ordinary skill in the art that the analytemonitoring system 100 may include one or more sensor 101, transmitterunit 102, communication link 103, and data processing terminal 105.Moreover, within the scope of the present disclosure, the analytemonitoring system 100 may be a continuous monitoring system, orsemi-continuous, or a discrete monitoring system. In a multi-componentenvironment, each device is configured to be uniquely identified by eachof the other devices in the system so that communication conflict isreadily resolved between the various components within the analytemonitoring system 100.

In one embodiment of the present disclosure, the sensor 101 isphysically positioned in or on the body of a user whose analyte level isbeing monitored. The sensor 101 may be configured to continuously samplethe analyte level of the user and convert the sampled analyte level intoa corresponding data signal for transmission by the transmitter unit102. In one embodiment, the transmitter unit 102 is coupled to thesensor 101 so that both devices are positioned on the user's body, withat least a portion of the analyte sensor 101 positioned transcutaneouslyunder the skin layer of the user. The transmitter unit 102 performs dataprocessing such as filtering and encoding on data signals, each of whichcorresponds to a sampled analyte level of the user, for transmission tothe primary receiver unit 104 via the communication link 103.

In one embodiment, the analyte monitoring system 100 is configured as aone-way RF communication path from the transmitter unit 102 to theprimary receiver unit 104. In such embodiment, the transmitter unit 102transmits the sampled data signals received from the sensor 101 withoutacknowledgement from the primary receiver unit 104 that the transmittedsampled data signals have been received. For example, the transmitterunit 102 may be configured to transmit the encoded sampled data signalsat a fixed rate (e.g., at one minute intervals) after the completion ofthe initial power on procedure. Likewise, the primary receiver unit 104may be configured to detect such transmitted encoded sampled datasignals at predetermined time intervals. Alternatively, the analytemonitoring system 100 may be configured with a bi-directional RF (orotherwise) communication between the transmitter unit 102 and theprimary receiver unit 104.

Additionally, in one aspect, the primary receiver unit 104 may includetwo sections. The first section is an analog interface section that isconfigured to communicate with the transmitter unit 102 via thecommunication link 103. In one embodiment, the analog interface sectionmay include an RF receiver and an antenna for receiving and amplifyingthe data signals from the transmitter unit 102, which are thereafter,demodulated with a local oscillator and filtered through a band-passfilter. The second section of the primary receiver unit 104 is a dataprocessing section which is configured to process the data signalsreceived from the transmitter unit 102 such as by performing datadecoding, error detection and correction, data clock generation, anddata bit recovery.

In operation, upon completing the power-on procedure, the primaryreceiver unit 104 is configured to detect the presence of thetransmitter unit 102 within its range based on, for example, thestrength of the detected data signals received from the transmitter unit102 or a predetermined transmitter identification information. Uponsuccessful synchronization with the corresponding transmitter unit 102,the primary receiver unit 104 is configured to begin receiving from thetransmitter unit 102 data signals corresponding to the user's detectedanalyte level. More specifically, the primary receiver unit 104 in oneembodiment is configured to perform synchronized time hopping with thecorresponding synchronized transmitter unit 102 via the communicationlink 103 to obtain the user's detected analyte level.

Referring again to FIG. 1, the data processing terminal 105 may includea personal computer, a portable computer such as a laptop or a handhelddevice (e.g., personal digital assistants (PDAs)), and the like, each ofwhich may be configured for data communication with the receiver via awired or a wireless connection. Additionally, the data processingterminal 105 may further be connected to a data network (not shown) forstoring, retrieving and updating data corresponding to the detectedanalyte level of the user.

Within the scope of the present disclosure, the data processing terminal105 may include an infusion device such as an insulin infusion pump orthe like, which may be configured to administer insulin to patients, andwhich may be configured to communicate with the receiver unit 104 forreceiving, among others, the measured analyte level. Alternatively, thereceiver unit 104 may be configured to integrate an infusion devicetherein so that the receiver unit 104 is configured to administerinsulin therapy to patients, for example, for administering andmodifying basal profiles, as well as for determining appropriate bolusesfor administration based on, among others, the detected analyte levelsreceived from the transmitter unit 102.

Additionally, the transmitter unit 102, the primary receiver unit 104and the data processing terminal 105 may each be configured forbi-directional wireless communication such that each of the transmitterunit 102, the primary receiver unit 104 and the data processing terminal105 may be configured to communicate (that is, transmit data to andreceive data from) with each other via a wireless communication link.More specifically, the data processing terminal 105 may in oneembodiment be configured to receive data directly from the transmitterunit 102 via a communication link, where the communication link, asdescribed above, may be configured for bi-directional communication.

In this embodiment, the data processing terminal 105 which may includean insulin pump, may be configured to receive the analyte signals fromthe transmitter unit 102, and thus, incorporate the functions of thereceiver unit 104 including data processing for managing the patient'sinsulin therapy and analyte monitoring. In one embodiment, thecommunication link 103 may include one or more of an RF communicationprotocol, an infrared communication protocol, a Bluetooth® enabledcommunication protocol, an 802.11x wireless communication protocol, aZigbee® transmission protocol, or an equivalent wireless communicationprotocol which would allow secure, wireless communication of severalunits (for example, per HIPAA requirements) while avoiding potentialdata collision and interference.

FIG. 2 is a block diagram of the transmitter of the data monitoring anddetection system shown in FIG. 1 in accordance with one embodiment ofthe present disclosure. Referring to the Figure, the transmitter unit102 in one embodiment includes an analog interface 201 configured tocommunicate with the sensor 101 (FIG. 1), a user input 202, and atemperature detection section 203, each of which is operatively coupledto a transmitter processor 204 such as a central processing unit (CPU).

Further shown in FIG. 2 are a transmitter serial communication section205 and an RF transmitter 206, each of which is also operatively coupledto the transmitter processor 204. Moreover, a power supply 207 such as abattery is also provided in the transmitter unit 102 to provide thenecessary power for the transmitter unit 102. Additionally, as can beseen from the Figure, clock 208 is provided to, among others, supplyreal time information to the transmitter processor 204.

As can be seen from FIG. 2, the sensor 101 (FIG. 1) is provided fourcontacts, three of which are electrodes—work electrode (W) 210, guardcontact (G) 211, reference electrode (R) 212, and counter electrode (C)213, each operatively coupled to the analog interface 201 of thetransmitter unit 102. In one embodiment, each of the work electrode (W)210, guard contact (G) 211, reference electrode (R) 212, and counterelectrode (C) 213 may be made using a conductive material that is eitherprinted or etched, for example, such as carbon which may be printed, ormetal foil (e.g., gold) which may be etched, or alternatively providedon a substrate material using laser or photolithography.

In one embodiment, a unidirectional input path is established from thesensor 101 (FIG. 1) and/or manufacturing and testing equipment to theanalog interface 201 of the transmitter unit 102, while a unidirectionaloutput is established from the output of the RF transmitter 206 of thetransmitter unit 102 for transmission to the primary receiver unit 104.In this manner, a data path is shown in FIG. 2 between theaforementioned unidirectional input and output via a dedicated link 209from the analog interface 201 to serial communication section 205,thereafter to the processor 204, and then to the RF transmitter 206. Assuch, in one embodiment, via the data path described above, thetransmitter unit 102 is configured to transmit to the primary receiverunit 104 (FIG. 1), via the communication link 103 (FIG. 1), processedand encoded data signals received from the sensor 101 (FIG. 1).Additionally, the unidirectional communication data path between theanalog interface 201 and the RF transmitter 206 discussed above allowsfor the configuration of the transmitter unit 102 for operation uponcompletion of the manufacturing process as well as for directcommunication for diagnostic and testing purposes.

As discussed above, the transmitter processor 204 is configured totransmit control signals to the various sections of the transmitter unit102 during the operation of the transmitter unit 102. In one embodiment,the transmitter processor 204 also includes a memory (not shown) forstoring data such as the identification information for the transmitterunit 102, as well as the data signals received from the sensor 101. Thestored information may be retrieved and processed for transmission tothe primary receiver unit 104 under the control of the transmitterprocessor 204. Furthermore, the power supply 207 may include acommercially available battery.

The transmitter unit 102 is also configured such that the power supplysection 207 is capable of providing power to the transmitter for aminimum of about three months of continuous operation after having beenstored for about eighteen months in a low-power (non-operating) mode. Inone embodiment, this may be achieved by the transmitter processor 204operating in low power modes in the non-operating state, for example,drawing no more than approximately 1 μA of current. Indeed, in oneembodiment, the final step during the manufacturing process of thetransmitter unit 102 may place the transmitter unit 102 in the lowerpower, non-operating state (i.e., post-manufacture sleep mode). In thismanner, the shelf life of the transmitter unit 102 may be significantlyimproved. Moreover, as shown in FIG. 2, while the power supply unit 207is shown as coupled to the processor 204, and as such, the processor 204is configured to provide control of the power supply unit 207, it shouldbe noted that within the scope of the present disclosure, the powersupply unit 207 is configured to provide the necessary power to each ofthe components of the transmitter unit 102 shown in FIG. 2.

Referring back to FIG. 2, the power supply section 207 of thetransmitter unit 102 in one embodiment may include a rechargeablebattery unit that may be recharged by a separate power supply rechargingunit (for example, provided in the receiver unit 104) so that thetransmitter unit 102 may be powered for a longer period of usage time.Moreover, in one embodiment, the transmitter unit 102 may be configuredwithout a battery in the power supply section 207, in which case thetransmitter unit 102 may be configured to receive power from an externalpower supply source (for example, a battery) as discussed in furtherdetail below.

Referring yet again to FIG. 2, the temperature detection section 203 ofthe transmitter unit 102 is configured to monitor the temperature of theskin near the sensor insertion site. The temperature reading is used toadjust the analyte readings obtained from the analog interface 201. TheRF transmitter 206 of the transmitter unit 102 may be configured foroperation in the frequency band of 315 MHz to 322 MHz, for example, inthe United States. Further, in one embodiment, the RF transmitter 206 isconfigured to modulate the carrier frequency by performing FrequencyShift Keying and Manchester encoding. In one embodiment, the datatransmission rate is 19,200 symbols per second, with a minimumtransmission range for communication with the primary receiver unit 104.

Referring yet again to FIG. 2, also shown is a leak detection circuit214 coupled to the guard contact (G) 211 and the processor 204 in thetransmitter unit 102 of the data monitoring and management system 100.The leak detection circuit 214 in accordance with one embodiment of thepresent disclosure may be configured to detect leakage current in thesensor 101 to determine whether the measured sensor data is corrupt orwhether the measured data from the sensor 101 is accurate.

FIG. 3 is a block diagram of the receiver/monitor unit of the datamonitoring and management system shown in FIG. 1 in accordance with oneembodiment of the present disclosure. Referring to FIG. 3, the primaryreceiver unit 104 includes a blood glucose test strip interface 301, anRF receiver 302, a user input 303, a temperature detection section 304,and a clock 305, each of which is operatively coupled to a receiverprocessor 307. As can be further seen from the Figure, the primaryreceiver unit 104 also includes a power supply 306 operatively coupledto a power conversion and monitoring section 308. Further, the powerconversion and monitoring section 308 is also coupled to the receiverprocessor 307. Moreover, also shown are a receiver serial communicationsection 309, and an output 310, each operatively coupled to the receiverprocessor 307.

In one embodiment, the test strip interface 301 includes a glucose leveltesting portion to receive a manual insertion of a glucose test strip,and thereby determine and display the glucose level of the test strip onthe output 310 of the primary receiver unit 104. This manual testing ofglucose can be used to calibrate sensor 101. The RF receiver 302 isconfigured to communicate, via the communication link 103 (FIG. 1) withthe RF transmitter 206 of the transmitter unit 102, to receive encodeddata signals from the transmitter unit 102 for, among others, signalmixing, demodulation, and other data processing. The input 303 of theprimary receiver unit 104 is configured to allow the user to enterinformation into the primary receiver unit 104 as needed. In one aspect,the input 303 may include one or more keys of a keypad, atouch-sensitive screen, or a voice-activated input command unit. Thetemperature detection section 304 is configured to provide temperatureinformation of the primary receiver unit 104 to the receiver processor307, while the clock 305 provides, among others, real time informationto the receiver processor 307.

Each of the various components of the primary receiver unit 104 shown inFIG. 3 is powered by the power supply 306 which, in one embodiment,includes a battery. Furthermore, the power conversion and monitoringsection 308 is configured to monitor the power usage by the variouscomponents in the primary receiver unit 104 for effective powermanagement and to alert the user, for example, in the event of powerusage which renders the primary receiver unit 104 in sub-optimaloperating conditions. An example of such sub-optimal operating conditionmay include, for example, operating the vibration output mode (asdiscussed below) for a period of time thus substantially draining thepower supply 306 while the processor 307 (thus, the primary receiverunit 104) is turned on. Moreover, the power conversion and monitoringsection 308 may additionally be configured to include a reverse polarityprotection circuit such as a field effect transistor (FET) configured asa battery activated switch.

The serial communication section 309 in the primary receiver unit 104 isconfigured to provide a bi-directional communication path from thetesting and/or manufacturing equipment for, among others,initialization, testing, and configuration of the primary receiver unit104. Serial communication section 309 can also be used to upload data toa computer, such as time-stamped blood glucose data. The communicationlink with an external device (not shown) can be made, for example, bycable, infrared (IR) or RF link. The output 310 of the primary receiverunit 104 is configured to provide, among others, a graphical userinterface (GUI) such as a liquid crystal display (LCD) for displayinginformation. Additionally, the output 310 may also include an integratedspeaker for outputting audible signals as well as to provide vibrationoutput as commonly found in handheld electronic devices, such as mobiletelephones presently available. In a further embodiment, the primaryreceiver unit 104 also includes an electro-luminescent lamp configuredto provide backlighting to the output 310 for output visual display indark ambient surroundings.

Referring back to FIG. 3, the primary receiver unit 104 in oneembodiment may also include a storage section such as a programmable,non-volatile memory device as part of the processor 307, or providedseparately in the primary receiver unit 104, operatively coupled to theprocessor 307. The processor 307 is further configured to performManchester decoding as well as error detection and correction upon theencoded data signals received from the transmitter unit 102 via thecommunication link 103.

In a further embodiment, the one or more of the transmitter unit 102,the primary receiver unit 104, secondary receiver unit 106, or the dataprocessing terminal/infusion section 105 may be configured to receivethe blood glucose value wirelessly over a communication link from, forexample, a glucose meter. In still a further embodiment, the user orpatient manipulating or using the analyte monitoring system 100 (FIG. 1)may manually input the blood glucose value using, for example, a userinterface (for example, a keyboard, keypad, and the like) incorporatedin the one or more of the transmitter unit 102, the primary receiverunit 104, secondary receiver unit 106, or the data processingterminal/infusion section 105.

Additional detailed description of the continuous analyte monitoringsystem, and its various components including the functional descriptionsof the transmitter are provided in U.S. Pat. No. 6,175,752 issued Jan.16, 2001 entitled “Analyte Monitoring Device and Methods of Use”, and inU.S. application Ser. No. 10/745,878 filed Dec. 26, 2003, now U.S. Pat.No. 7,811,231, entitled “Continuous Glucose Monitoring System andMethods of Use”, each assigned to the Assignee of the presentapplication, and each of which are incorporated herein by reference forall purposes.

FIGS. 4A-4B illustrate a perspective view and a cross sectional view,respectively of an analyte sensor in accordance with one embodiment ofthe present disclosure. Referring to FIG. 4A, a perspective view of asensor 400, the major portion of which is above the surface of the skin410, with an insertion tip 430 penetrating through the skin and into thesubcutaneous space 420 in contact with the user's biofluid such asinterstitial fluid. Contact portions of a working electrode 401, areference electrode 402, and a counter electrode 403 can be seen on theportion of the sensor 400 situated above the skin surface 410. Workingelectrode 401, a reference electrode 402, and a counter electrode 403can be seen at the end of the insertion tip 430.

Referring now to FIG. 4B, a cross sectional view of the sensor 400 inone embodiment is shown. In particular, it can be seen that the variouselectrodes of the sensor 400 as well as the substrate and the dielectriclayers are provided in a stacked or layered configuration orconstruction. For example, as shown in FIG. 4B, in one aspect, thesensor 400 (such as the sensor 101 FIG. 1), includes a substrate layer404, and a first conducting layer 401 such as a carbon trace disposed onat least a portion of the substrate layer 404, and which may comprisethe working electrode. Also shown disposed on at least a portion of thefirst conducting layer 401 is a sensing layer 408.

Referring back to FIG. 4B, a first insulation layer such as a firstdielectric layer 405 is disposed or stacked on at least a portion of thefirst conducting layer 401, and further, a second conducting layer 409such as another carbon trace may be disposed or stacked on top of atleast a portion of the first insulation layer (or dielectric layer) 405.As shown in FIG. 4B, the second conducting layer 409 may comprise thereference electrode 402, and in one aspect, may include a layer ofsilver/silver chloride (Ag/AgCl).

Referring still again to FIG. 4B, a second insulation layer 406 such asa dielectric layer in one embodiment may be disposed or stacked on atleast a portion of the second conducting layer 409. Further, a thirdconducting layer 403 which may include carbon trace and that maycomprise the counter electrode 403 may in one embodiment be disposed onat least a portion of the second insulation layer 406. Finally, a thirdinsulation layer 407 is disposed or stacked on at least a portion of thethird conducting layer 403. In this manner, the sensor 400 may beconfigured in a stacked or layered construction or configuration suchthat at least a portion of each of the conducting layers is separated bya respective insulation layer (for example, a dielectric layer).

Additionally, within the scope of the present disclosure, some or all ofthe electrodes 401, 402, 403 may be provided on the same side of thesubstrate 404 in a stacked construction as described above, oralternatively, may be provided in a co-planar manner such that eachelectrode is disposed on the same plane on the substrate 404, however,with a dielectric material or insulation material disposed between theconducting layers/electrodes. Furthermore, in still another aspect ofthe present disclosure, the one or more conducting layers such as theelectrodes 401, 402, 403 may be disposed on opposing sides of thesubstrate 404.

Referring back to the Figures, in one embodiment, the transmitter unit102 (FIG. 1) is configured to detect the current signal from the sensor101 (FIG. 1) and the skin temperature near the sensor 101, which arepreprocessed by, for example, the transmitter processor 204 (FIG. 2) andtransmitted to the receiver unit (for example, the primary receiver unit104 (FIG. 1)) periodically at a predetermined time interval, such as forexample, but not limited to, once per minute, once every two minutes,once every five minutes, or once every ten minutes. Additionally, thetransmitter unit 102 may be configured to perform sensor insertiondetection and data quality analysis, information pertaining to which arealso transmitted to the receiver unit 104 periodically at thepredetermined time interval. In turn, the receiver unit 104 may beconfigured to perform, for example, skin temperature compensation aswell as calibration of the sensor data received from the transmitterunit 102.

For example, in one aspect, the transmitter unit 102 may be configuredto oversample the sensor signal at a nominal rate of four samples persecond, which allows the analyte anti-aliasing filter in the transmitterunit 102 to attenuate noise (for example, due to effects resulting frommotion or movement of the sensor after placement) at frequencies above 2Hz. More specifically, in one embodiment, the transmitter processor 204may be configured to include a digital filter to reduce aliasing noisewhen decimating the four Hz sampled sensor data to once per minutesamples for transmission to the receiver unit 104. As discussed infurther detail below, in one aspect, a two stage Kaiser FIR filter maybe used to perform the digital filtering for anti-aliasing. While KaiserFIR filter may be used for digital filtering of the sensor signals,within the scope of the present disclosure, other suitable filters maybe used to filter the sensor signals.

In one aspect, the temperature measurement section 203 of thetransmitter unit 102 may be configured to measure once per minute the onskin temperature near the analyte sensor at the end of the minutesampling cycle of the sensor signal. Within the scope of the presentdisclosure, different sample rates may be used which may include, forexample, but not limited to, measuring the on skin temperature for each30 second periods, each two minute periods, and the like. Additionally,as discussed above, the transmitter unit 102 may be configured to detectsensor insertion, sensor signal settling after sensor insertion, andsensor removal, in addition to detecting for sensor—transmitter systemfailure modes and sensor signal data integrity. Again, this informationis transmitted periodically by the transmitter unit 102 to the receiverunit 104 along with the sampled sensor signals at the predetermined timeintervals.

Referring again to the Figures, as the analyte sensor measurements areaffected by the temperature of the tissue around the transcutaneouslypositioned sensor 101, in one aspect, compensation of the temperaturevariations and effects on the sensor signals are provided fordetermining the corresponding glucose value. Moreover, the ambienttemperature around the sensor 101 may affect the accuracy of the on skintemperature measurement and ultimately the glucose value determined fromthe sensor signals. Accordingly, in one aspect, a second temperaturesensor is provided in the transmitter unit 102 away from the on skintemperature sensor (for example, physically away from the temperaturemeasurement section 203 of the transmitter unit 102), so as to providecompensation or correction of the on skin temperature measurements dueto the ambient temperature effects. In this manner, the accuracy of theestimated glucose value corresponding to the sensor signals may beattained.

In one aspect, the processor 204 of the transmitter unit 102 may beconfigured to include the second temperature sensor, and which islocated closer to the ambient thermal source within the transmitter unit102. In other embodiments, the second temperature sensor may be locatedat a different location within the transmitter unit 102 housing wherethe ambient temperature within the housing of the transmitter unit 102may be accurately determined.

Referring now to FIG. 5, in one aspect, an ambient temperaturecompensation routine for determining the on-skin temperature level foruse in the glucose estimation determination based on the signalsreceived from the sensor 101. Referring to FIG. 5, for each sampledsignal from the sensor 101, a corresponding measured temperatureinformation is received (510), for example, by the processor 204 fromthe temperature measurement section 203 (which may include, for example,a thermistor provided in the transmitter unit 102). In addition, asecond temperature measurement is obtained (520), for example, includinga determination of the ambient temperature level using a secondtemperature sensor provided within the housing the transmitter unit 102.

In one aspect, based on a predetermined ratio of thermal resistancesbetween the temperature measurement section 203 and the secondtemperature sensor (located, for example, within the processor 204 ofthe transmitter unit 102), and between the temperature measurementsection 203 and the skin layer on which the transmitter unit 102 isplaced and coupled to the sensor 101, ambient temperature compensationmay be performed (530), to determine the corresponding ambienttemperature compensated on skin temperature level (540). In oneembodiment, the predetermined ratio of the thermal resistances may beapproximately 0.2. However, within the scope of the present disclosure,this thermal resistance ratio may vary according to the design of thesystem, for example, based on the size of the transmitter unit 102housing, the location of the second temperature sensor within thehousing of the transmitter unit 102, and the like.

With the ambient temperature compensated on-skin temperatureinformation, the corresponding glucose value from the sampled analytesensor signal may be determined.

Referring again to FIG. 2, the processor 204 of the transmitter unit 102may include a digital anti-aliasing filter. Using analog anti-aliasingfilters for a one minute measurement data sample rate would require alarge capacitor in the transmitter unit 102 design, and which in turnimpacts the size of the transmitter unit 102. As such, in one aspect,the sensor signals may be oversampled (for example, at a rate of 4 timesper second), and then the data is digitally decimated to derive aone-minute sample rate.

As discussed above, in one aspect, the digital anti-aliasing filter maybe used to remove, for example, signal artifacts or otherwiseundesirable aliasing effects on the sampled digital signals receivedfrom the analog interface 201 of the transmitter unit 102. For example,in one aspect, the digital anti-aliasing filter may be used toaccommodate decimation of the sensor data from approximately four Hzsamples to one-minute samples. In one aspect, a two stage FIR filter maybe used for the digital anti-aliasing filter, which includes improvedresponse time, pass band and stop band properties.

Referring to FIG. 6, a routine for digital anti-aliasing filtering isshown in accordance with one embodiment. As shown, in one embodiment, ateach predetermined time period such as every minute, the analog signalfrom the analog interface 201 corresponding to the monitored analytelevel received from the sensor 101 (FIG. 1) is sampled (610). Forexample, at every minute, in one embodiment, the signal from the analoginterface 201 is over-sampled at approximately 4 Hz. Thereafter, thefirst stage digital filtering on the over-sampled data is performed(620), where, for example, a ⅙ down-sampling from 246 samples to 41samples is performed, and the resulting 41 samples is furtherdown-sampled at the second stage digital filtering (630) such that, forexample, a 1/41 down-sampling is performed from 41 samples (from thefirst stage digital filtering), to a single sample. Thereafter, thefilter is reset (640), and the routine returns to the beginning for thenext minute signal received from the analog interface 201.

While the use of FIR filter, and in particular the use of Kaiser FIRfilter, is within the scope of the present disclosure, other suitablefilters, such as FIR filters with different weighting schemes or IIRfilters, may be used.

Referring yet again to the Figures, the transmitter unit 102 may beconfigured in one embodiment to periodically perform data quality checksincluding error condition verifications and potential error conditiondetections, and also to transmit the relevant information related to oneor more data quality, error condition or potential error conditiondetection to the receiver unit 104 with the transmission of themonitored sensor data. For example, in one aspect, a state machine maybe used in conjunction with the transmitter unit 102 and which may beconfigured to be updated four times per second, the results of which aretransmitted to the receiver unit 104 every minute.

In particular, using the state machine, the transmitter unit 102 may beconfigured to detect one or more states that may indicate when a sensoris inserted, when a sensor is removed from the user, and further, mayadditionally be configured to perform related data quality checks so asto determine when a new sensor has been inserted or transcutaneouslypositioned under the skin layer of the user and has settled in theinserted state such that the data transmitted from the transmitter unit102 does not compromise the integrity of signal processing performed bythe receiver unit 104 due to, for example, signal transients resultingfrom the sensor insertion.

That is, when the transmitter unit 102 detects low or no signal from thesensor 101, which is followed by detected signals from the sensor 101that is above a given signal, the processor 204 may be configured toidentify such transition is monitored signal levels and associate with apotential sensor insertion state. Alternatively, the transmitter unit102 may be configured to detect the signal level above anotherpredetermined threshold level, which is followed by the detection of thesignal level from the sensor 101 that falls below the predeterminedthreshold level. In such a case, the processor 204 may be configured toassociate or identify such transition or condition in the monitoredsignal levels as a potential sensor removal state.

Accordingly, when either of potential sensor insertion state orpotential sensor removal state is detected by the transmitter unit 102,this information is transmitted to the receiver unit 104, and in turn,the receiver unit may be configured to prompt the user for confirmationof either of the detected potential sensor related state. In anotheraspect, the sensor insertion state or potential sensor removal state maybe detected or determined by the receiver unit based on one or moresignals received from the transmitter unit 102. For example, similar toan alarm condition or a notification to the user, the receiver unit 104may be configured to display a request or a prompt on the display or anoutput unit of the receiver unit 104 a text and/or other suitablenotification message to inform the user to confirm the state of thesensor 101.

For example, the receiver unit 104 may be configured to display thefollowing message: “New Sensor Inserted?” or a similar notification inthe case where the receiver unit 104 receives one or more signals fromthe transmitter unit 102 associated with the detection of the signallevel below the predetermined threshold level for the predefined periodof time, followed by the detection of the signal level from the sensor101 above another predetermined threshold level for another predefinedperiod of time. Additionally, the receiver unit 104 may be configured todisplay the following message: “Sensor Removed?” or a similarnotification in the case where the receiver unit 104 received one ormore signals from the transmitter unit 102 associated with the detectionof the signal level from the sensor 101 that is above anotherpredetermined threshold level for another predefined period of time,which is followed by the detection of the signal level from the sensor101 that falls below the predetermined threshold level for thepredefined period of time.

Based on the user confirmation received, the receiver unit 104 may befurther configured to execute or perform additional related processingand routines in response to the user confirmation or acknowledgement.For example, when the user confirms, using the user interfaceinput/output mechanism of the receiver unit 104, for example, that a newsensor has been inserted, the receiver unit 104 may be configured toinitiate new sensor insertion related routines including, such as, forexample, a sensor calibration routine including, for example,calibration timer, sensor expiration timer and the like. Alternatively,when the user confirms or it is determined that the sensor 101 is notproperly positioned or otherwise removed from the insertion site, thereceiver unit 104 may be accordingly configured to perform relatedfunctions such as, for example, stop displaying of the glucosevalues/levels, or deactivating the alarm monitoring conditions.

On the other hand, in response to the potential sensor insertionnotification generated by the receiver unit 104, if the user confirmsthat no new sensor has been inserted, then the receiver unit 104 in oneembodiment is configured to assume that the sensor 101 is in acceptableoperational state, and continues to receive and process signals from thetransmitter unit 102.

In this manner, in cases, for example, when there is momentary movementor temporary dislodging of the sensor 101 from the initially positionedtranscutaneous state, or when one or more of the contact points betweensensor 101 and the transmitter unit 102 are temporarily disconnected,but otherwise, the sensor 101 is operational and within its useful life,the routine above provides an option to the user to maintain the usageof the sensor 101, without replacing the sensor 101 prior to theexpiration of its useful life. In this manner, in one aspect, falsepositive indications of sensor 101 failure may be identified andaddressed.

For example, FIG. 7 is a flowchart illustrating actual or potentialsensor insertion or removal detection routine in accordance with oneembodiment of the present disclosure. Referring to the Figure, thecurrent analyte related signal is first compared to a predeterminedsignal characteristic (710). In one aspect, the predetermined signalcharacteristic may include one of a signal level transition from below afirst predetermined level (for example, but not limited to 18 ADC(analog to digital converter) counts) to above the first predeterminedlevel, a signal level transition from above a second predetermined level(for example, but not limited to 9 ADC counts) to below the secondpredetermined level, a transition from below a predetermined signal rateof change threshold to above the predetermined signal rate of changethreshold, and a transition from above the predetermined signal rate ofchange threshold to below the predetermined signal rate of changethreshold.

In this manner, in one aspect of the present disclosure, based on atransition state of the received analyte related signals, it may bepossible to determine the state of the analyte sensor (720), and basedon which, the user or the patient may confirm whether the analyte sensoris in the desired or proper position, has been temporarily dislocated,or otherwise, removed from the desired insertion site so as to require anew analyte sensor.

In this manner, in one aspect, when the monitored signal from the sensor101 crosses a transition level (730) (for example, from no or low signallevel to a high signal level, or vice versa), the transmitter unit 102may be configured to generate an appropriate output data associated withthe sensor signal transition (740), for transmission to the receiverunit 104 (FIG. 1). Additionally, as discussed in further detail below,in another embodiment, the determination of whether the sensor 101 hascrossed a transition level may be determined by the receiver/monitorunit 104/106 based, at least in part on the one or more signals receivedfrom the transmitter unit 102.

FIG. 8 is a flowchart illustrating receiver unit processingcorresponding to the actual or potential sensor insertion or removaldetection routine of FIG. 7 in accordance with one embodiment of thepresent disclosure. Referring now to FIG. 8, when the receiver unit 104receives the generated output data from the transmitter unit 102 (810),a corresponding operation state is associated with the received outputdata (820), for example, related to the operational state of the sensor101. Moreover, a notification associated with the sensor operation stateis generated and output to the user on the display unit or any othersuitable output segment of the receiver unit 104 (830). When a userinput signal is received in response to the notification associated withthe sensor state operation state (840), the receiver unit 104 isconfigured to execute one or more routines associated with the receiveduser input signal (850).

That is, as discussed above, in one aspect, if the user confirms thatthe sensor 101 has been removed, the receiver unit 104 may be configuredto terminate or deactivate alarm monitoring and glucose displayingfunctions. On the other hand, if the user confirms that a new sensor 101has been positioned or inserted into the user, then the receiver unit104 may be configured to initiate or execute routines associated withthe new sensor insertion, such as, for example, calibration procedures,establishing calibration timer, and establishing sensor expirationtimer.

In a further embodiment, based on the detected or monitored signaltransition, the receiver/monitor unit may be configured to determine thecorresponding sensor state without relying upon the user input orconfirmation signal associated with whether the sensor is dislocated orremoved from the insertion site, or otherwise, operating properly.

FIG. 9 is a flowchart illustrating data processing corresponding to theactual or potential sensor insertion or removal detection routine inaccordance with another embodiment of the present disclosure. Referringto FIG. 9, a current analyte related signal is received and compared toa predetermined signal characteristic (910). Thereafter, an operationalstate associated with an analyte monitoring device such as, for example,the sensor 101 (FIG. 1) is retrieved (920) from a storage unit orotherwise resident in, for example, a memory of the receiver/monitorunit. Additionally, a prior analyte related signal is also retrievedfrom the storage unit, and compared to the current analyte relatedsignal received (930). An output data is generated which is associatedwith the operational state (940), and which at least in part is based onthe one or more of the received current analyte related signal and theretrieved prior analyte related signal.

Referring again to FIG. 9, when the output data is generated, acorresponding user input command or signal is received in response tothe generated output data (950), which may include one or more of aconfirmation, verification, or rejection of the operational staterelated to the analyte monitoring device.

FIG. 10 is a flowchart illustrating a concurrent passive notificationroutine in the data receiver/monitor unit of the data monitoring andmanagement system of FIG. 1 in accordance with one embodiment of thepresent disclosure. Referring to FIG. 10, a predetermined routine isexecuted for a predetermined time period to completion (1010). Duringthe execution of the predetermined routine, an alarm condition isdetected (1020), and when the alarm or alert condition is detected, afirst indication associated with the detected alarm or alert conditionis output concurrent to the execution of the predetermined routine(1030).

That is, in one embodiment, when a predefined routine is being executed,and an alarm or alert condition is detected, a notification is providedto the user or patient associated with the detected alarm or alertcondition, but which does not interrupt or otherwise disrupt theexecution of the predefined routine. Referring back to FIG. 10, upontermination of the predetermined routine, another output or secondindication associated with the detected alarm condition is output ordisplayed (1040).

More specifically, in one aspect, the user interface notificationfeature associated with the detected alarm condition is output to theuser only upon the completion of an ongoing routine which was in theprocess of being executed when the alarm condition is detected. Asdiscussed above, when such alarm condition is detected during theexecution of a predetermined routine, a temporary alarm notificationsuch as, for example, a backlight indicator, a text output on the userinterface display or any other suitable output indication may beprovided to alert the user or the patient of the detected alarmcondition substantially in real time, but which does not disrupt anongoing routine.

Within the scope of the present disclosure, the ongoing routine or thepredetermined routine being executed may include one or more ofperforming a finger stick blood glucose test (for example, for purposesof periodically calibrating the sensor 101), or any other processes thatinterface with the user interface, for example, on the receiver/monitorunit 104/106 (FIG. 1) including, but not limited to the configuration ofdevice settings, review of historical data such as glucose data, alarms,events, entries in the data log, visual displays of data includinggraphs, lists, and plots, data communication management including RFcommunication administration, data transfer to the data processingterminal 105 (FIG. 1), or viewing one or more alarm conditions with adifferent priority in a preprogrammed or determined alarm ornotification hierarchy structure.

In this manner, in one aspect of the present disclosure, the detectionof one or more alarm conditions may be presented or notified to the useror the patient, without interrupting or disrupting an ongoing routine orprocess in, for example, the receiver/monitor unit 104/106 of the datamonitoring and management system 100 (FIG. 1).

Referring now back to the Figures, FIG. 11 is a flowchart illustrating adata quality verification routine in accordance with one embodiment ofthe present disclosure. Referring to FIG. 11, initially the data qualitystatus flags are cleared or initialized or reset (1110). Thereafter,data quality checks or verifications are performed, for example, asdescribed above (1120). Thereafter, data quality flag is generated andassociated with the data packet when data quality check has failed(1130). In one aspect, the generated data quality flag may be based ondata quality verification such that when the underlying condition beingverified is determined to be acceptable, the data quality flag mayreturn a value of zero (or one or more predetermined value).Alternatively, in the case where the underlying condition being verifiedis determined to be not within the acceptable criteria (or above theacceptable level), the associated data quality flag may return a valueof one (or one or more predetermined value associated with thedetermination of such condition).

Referring to FIG. 11, the data packet including the raw glucose data aswell as the data quality flags are transmitted, for example, to thereceiver/monitor unit 104/106 for further processing (1140). Asdescribed above, the data quality checks may be performed in thetransmitter unit 102 (FIG. 1) and/or in the receiver/monitor unit104/106 in the data monitoring and management system 100 (FIG. 1) in oneaspect of the present disclosure.

FIG. 12 is a flowchart illustrating a rate variance filtering routine inaccordance with one embodiment of the present disclosure. Referring toFIG. 12, when glucose related data is detected or received (1210), forexample, for each predetermined time intervals such as every minute,every five minutes or any other suitable time intervals, a plurality offiltered values based on the received or detected glucose related datais determined (1220). For example, as discussed above, in one aspect,using, for example, an FIR filter, or based on a weighted average, aplurality of filtered values for a 15 minute and two minute glucoserelated data including the currently received or detected glucoserelated are determined.

Referring back to FIG. 12, weighting associated with the plurality offiltered values is determined (1230). Thereafter, a rate of change ofthe glucose level based in part on the detected or received glucoserelated data is determined as well as a standard deviation of the rateof change based on the glucose related data (1240). Further, a weightedaverage associated with the current detected or monitored glucoserelated data is determined based on the plurality of filtered values andthe determined standard deviation of the rate of change and/or the rateof change of the glucose level (1250). For example, when the rate ofchange is determined to be high relative to the rate of changevariation, the filtered value based on the two minute data is weightedmore heavily. On the other hand, when the rate of change is determinedto be low relative to the rate of change variation, the filtered glucoserelated data includes the one of the plurality of filtered values basedon the 15 minute data which is weighted more heavily. In this manner, inone aspect, there is provided a rate variance filtering approach whichmay be configured to dynamically modify the weighting function or datafiltering to, for example, reduce undesirable variation in glucoserelated signals due to factors such as noise.

FIG. 13 is a flowchart illustrating a composite sensor sensitivitydetermination routine in accordance with one embodiment of the presentdisclosure. Referring to FIG. 13, during scheduled calibration timeperiods or otherwise manual calibration routines to calibrate theanalyte sensor, when a current blood glucose value is received ordetected (1310), a current or present sensitivity is determined based onthe detected blood glucose value (1320). For example, the currentsensitivity may be determined by taking a ratio of the current glucosesensor value and the detected blood glucose value.

Referring to FIG. 13, a prior sensitivity previously determined isretrieved, for example, from the storage unit (1330). In one aspect, theprior sensitivity may include a previous sensitivity determined during aprior sensor calibration event, or may be based on the nominal sensorsensitivity based on the sensor code from manufacturing, for example.Returning again to FIG. 13, a first weighted parameter is applied to thecurrent sensitivity, and a second weighted parameter is applied to theretrieved prior sensitivity (1340). For example, based on the timelapsed between the calibration event associated with the retrieved priorsensitivity value and the current calibration event (associated with thecurrent or received blood glucose value), the first and second weightedparameters may be modified (e.g., increased or decreased in value) toimprove accuracy.

Referring back to FIG. 13, based on applying the first and the secondweighted parameters to the current sensitivity and the retrieved priorsensitivity, a composite sensitivity associated with the analyte sensorfor the current calibration event is determined (1350). For example,using a time based approach, in one embodiment, the sensitivityassociated with the analyte sensor for calibration may be determined to,for example, reduce calibration errors or accommodate sensitivity drift.

FIG. 14 is a flowchart illustrating an outlier data point verificationroutine in accordance with one embodiment of the present disclosure.Referring to FIG. 14, and as discussed in detail above, in determiningcomposite sensitivity associated with the analyte sensor calibration, inone aspect, an outlier data point may be detected and accordinglycorrected. For example, in one aspect, two successive sensitivitiesassociated with two successive calibration events for the analyte sensoris compared (1410). If it is determined that the comparison between thetwo sensitivities are within a predetermined range (1420), the compositesensitivity for the current calibration of the analyte sensor isdetermined based on the two successive sensitivity values (1430), using,for example, the weighted approach described above.

Referring back to FIG. 14, if it is determined that the comparison ofthe two successive sensitivities results in the compared value beingoutside of the predetermined range, then the user may be prompted toenter or provide a new current blood glucose value (for example, using ablood glucose meter) (1440). Based on the new blood glucose valuereceived, an updated or new sensitivity associated with the analytesensor is determined (1450). Thereafter, the new or updated sensitivitydetermined is compared with the two prior sensitivities compared (at1420) to determine whether the new or updated sensitivity is within apredefined range of either of the two prior sensitivities (1460). If itis determined that the new or updated sensitivity of the analyte sensoris within the predefined range of either of the two prior successivesensitivities, a composite sensitivity is determined based on the new orupdated sensitivity and the one of the two prior successivesensitivities within the defined range of which the new or updatedsensitivity is determined (1470). On the other hand, if it is determinedthat the new or updated sensitivity is not within the predefined rangeof either of the two prior sensitivities, then the routine repeats andprompts the user to enter a new blood glucose value (1440).

FIG. 15 is a flowchart illustrating a sensor stability verificationroutine in accordance with one embodiment of the present disclosure.Referring to FIG. 15, and as discussed above, between predetermined orscheduled baseline calibration events to calibrate the sensor, theanalyte sensor sensitivity stability may be verified, to determine, forexample, if additional stability calibrations may be needed prior to thesubsequent scheduled baseline calibration event.

For example, referring to FIG. 15, in one embodiment, after the secondbaseline calibration event to calibrate the analyte sensor, the user maybe prompted to provide a new blood glucose value. With the current bloodglucose value received (1510), the current sensor sensitivity isdetermined (1520). Thereafter, the most recent stored sensor sensitivityvalue from prior calibration event is retrieved (for example, from astorage unit) (1530), and the determined current sensor sensitivity iscompared with the retrieved stored sensor sensitivity value to determinewhether the difference, if any, between the two sensitivity values arewithin a predefined range (1540).

Referring back to FIG. 15, if it is determined that the differencebetween the current and retrieved sensitivity values are within thepredefined range, then the stability associated with the sensorsensitivity is confirmed (1550), and no additional calibration isrequired prior to the subsequent scheduled baseline calibration event.On the other hand, if it is determined that the difference between thecurrent sensitivity and the retrieved prior sensitivity is not withinthe predefined range, then after a predetermined time period has lapsed(1560), the routine returns to the beginning and prompts the user toenter a new blood glucose value to perform the stability verificationroutine.

In this manner, in one aspect, the stability checks may be performedafter the outlier check is performed, and a new composite sensitivitydetermined as described above. Accordingly, in one aspect, analytesensor sensitivity may be monitored as the sensitivity attenuation isdissipating to, among others, improve accuracy of the monitored glucosedata and sensor stability.

FIG. 16 illustrates analyte sensor code determination in accordance withone embodiment. Referring to the Figure, a batch of predetermined numberof analyte sensors, for example, glucose sensors are selected during themanufacturing process (1610). The batch of predetermined number ofglucose sensors may be a set number, or a variable number depending uponother manufacturing or post-manufacturing parameters (for example, suchas testing, quality control verification, or packaging).

Referring to FIG. 16, the sensitivity of each selected glucose sensor isdetermined (1620). For example, in one aspect, in vitro sensitivitydetermination is performed for each selected glucose sensor to determinethe corresponding sensitivity. Thereafter, a variation between thedetermined sensitivity of each glucose sensor is determined (1630). Thatis, in one aspect, the determined in vitro sensitivity associated witheach selected glucose sensor is compared to a predefined variationtolerance level (1640).

In one aspect, if the variation of the sensitivity is greater than thepredefined variation tolerance level for one of the selected glucosesensors in the selected batch of predetermined number of glucose sensors(1660), then the entire batch or lot may be rejected and not used. Inanother aspect, the rejection of the selected batch of predeterminednumber of glucose sensors may be based on a predetermined number ofsensors within the selected batch that are associated with a sensitivityvalue that exceeds the predefined variation tolerance level. Forexample, in a batch of 30 glucose sensors, if 10 percent (or 3 sensors)has sensitivity that exceeds the predefined variation tolerance level,then the entire batch of 30 glucose sensors is rejected and not furtherprocessed during the manufacturing routine, for example, for use. Withinthe scope of the present disclosure, the number of sensors in theselected batch, or the number of sensors within the selected batch thatexceeds the predefined variation tolerance level to result in a failedbatch may be varied depending upon, for example, but not limited to,sensor manufacturing process, sensor testing routines, quality controlverification, or other parameters associated with sensor performanceintegrity.

Referring back to FIG. 16, if it is determined that the sensitivity ofthe selected glucose sensors are within the predefined variationtolerance level, a nominal sensitivity is determined for the batch ofthe predetermined number of glucose sensors (1650). Further, a sensorcode is associated with the determined nominal sensitivity for the batchof predetermined number of analyte sensors (1670).

In one aspect, the sensor code may be provided on the labeling for thebatch of glucose sensors for use by the patient or the user. Forexample, in one aspect, the analyte monitoring system may prompt theuser to enter the sensor code into the system (for example, to thereceiver unit 104/106 FIG. 1) after the sensor has been initiallypositioned in the patient and prior to the first sensor calibrationevent. In a further aspect, based on the sensor code, the analytemonitoring system may be configured to retrieve the nominal sensitivityassociated with the batch of predetermined number of sensors for, forexample, calibration of the transcutaneously positioned glucose sensor.

FIG. 17 illustrates an early user notification function associated withthe analyte sensor condition in one aspect of the present disclosure.Referring to FIG. 17, upon detection of the sensor insertion (1710), forexample, in fluid contact with the patient or user's analyte (e.g.,interstitial fluid), one or more adverse data condition occurrenceassociated with the patient or the user's analyte level is monitored(1720). Examples of the adverse data condition occurrence may include,for example, a persistent low sensor signal (for example, continuous fora predefined time period), identified data quality flags or identifiersassociated with erroneous or potentially inaccurate sensor signal levelor sensor condition (for example, dislodged or improperly positionedsensor).

Referring to FIG. 17, when it is determined that the monitored adversedata condition occurrence exceeds a predetermined number of occurrencesduring a predefined time period (1730), a notification is generated andprovided to the user to either replace the sensor, or to perform one ormore verifications to confirm, for example, but not limited to, that thesensor is properly inserted and positioned, so the transmitter unit isin proper contact with the sensor (1740).

On the other hand, if the number of adverse data condition occurrencehas not occurred during the predefined time period, in one aspect, theroutine continues to monitor for the occurrence of such condition duringthe set time period. In one aspect, the predetermined time period duringwhich the occurrence of adverse data condition occurrence may beapproximately one hour from the initial sensor positioning.Alternatively, this time period may be shorter or longer, depending uponthe particular system configuration.

In this manner, in the event that adverse condition related to thesensor is determined and persists for a given time period from theinitial sensor insertion, the user or the patient is notified to eitherreplace the sensor or to perform one or more troubleshooting steps tomake sure that the components of the analyte monitoring system arefunctioning properly. Indeed, in one aspect, when an adverse conditionrelated to the sensor is identified early on, the user is notinconvenienced by continuing to maintain the sensor in position eventhough the sensor may be defective or improperly positioned, or isassociated with one or more other adverse conditions that will not allowthe sensor to function properly.

FIG. 18 illustrates uncertainty estimation associated with glucose levelrate of change determination in one aspect of the present disclosure.Referring to FIG. 18, based on the monitored glucose level from theglucose sensor, a rate of change estimate of the glucose levelfluctuation is determined (1810). Further, an estimation of anuncertainty range or level associated with the determined rate of changeof the glucose level is determined (1820). That is, in one aspect, apredefined rate of uncertainty determination may be performed, such asfor example, a rate of change variance calculation. If the uncertaintydetermination is within a predetermined threshold level (1830), then anoutput is generated and/or provided to the user (1840).

For example, when it is determined that the determined uncertaintymeasure is within the threshold level, the analyte monitoring system maybe configured to display or output an indication to the user or thepatient, such as a glucose level trend indicator (for example, a visualtrend arrow or a distinctive audible alert (increasing or decreasingtone, etc)). On the other hand, if it is determined that the uncertaintymeasure related to the rate of change estimate exceeds the predeterminedthreshold, the determined rate of change of glucose level may berejected or discarded (or stored but not output to the user or thepatient). In one aspect, the uncertainty measure may include apredefined tolerance parameter associated with the accuracy of thedetermined rate of change of the monitored glucose level.

In one aspect, the uncertainty measure or the tolerance level related tothe rate of change of monitored glucose level may include, for example,but not limited to, corrupt or erroneous data associated with themonitored glucose level, unacceptably large number of missing dataassociated with the monitored glucose level, rate of acceleration ordeceleration of the monitored glucose level that exceeds a defined oracceptable threshold level, or any other parameters that may contributeto potential inaccuracy in the determined rate of change of themonitored glucose level.

Accordingly, in one aspect, the accuracy of the analyte monitoringsystem may be maintained by, for example, disabling the output functionassociated with the rate of change determination related to themonitored glucose level, so that the user or the patient does not takecorrective actions based on potentially inaccurate information. That is,as discussed above, in the event when it is determined that thedetermined uncertainty measure or parameter exceeds an acceptabletolerance range, the output function on the receiver unit 104/106 in theanalyte monitoring system 100 may be disabled temporarily, or until theuncertainty measure of parameter related to the rate of change of theglucose level being monitored is within the acceptable tolerance range.

When the monitored rate of change of the glucose level is steady (orwithin a defined range) and medically significant with respect to themonitored glucose measurement, a prediction of future or anticipatedglucose level may be considered reliable based on the determined rate ofchange level. However, the monitored glucose level time series is suchthat the determined rate of change estimate may be less certain.

Accordingly, in one aspect, the present disclosure accounts for the rateof change estimates having varying degrees of certainty. Since clinicaltreatment decisions may be made based on these estimates, it isimportant to discount, or not display or output to the user, thedetermined rate of change estimates with a high degree of uncertainty.

In one aspect, the rate of change value and its uncertainty determine aprobability distribution. This distribution may be assumed to beGaussian, for example. Within the scope of the present disclosure, theuncertainty measure may be calculated in various ways. In oneembodiment, it may include a standard deviation determination. Anotherpossibility is to use the coefficient of variation (CV), which is thestandard deviation of the rate of change divided by the rate of change.A combination of these uncertainty measures may also be used.

In one aspect, various ranges of rates of change may be combined intobins. For example, bin edges at ±2 mg/dL and at ±1 mg/dL may be definedin one embodiment resulting in five bins. Each bin may be represented bya position of a trend arrow indicator, associated with the monitoredglucose level. When the rate of change is included in one of thedetermined bins, the associated trend arrow position may be displayed.

Further, the presence of uncertainty may modify the trend arrow positionthat is displayed to the user or the patient. In one aspect, adetermination that involves the uncertainty measure results in a metricvalue which may be a simple comparison of the uncertainty value to apredefined threshold. There are also other possible metrics. Anotherapproach may use a different predefined threshold value for each bin.

In one aspect, an unacceptable metric value may cause no trend arrowindicator to be displayed. Alternatively, this condition may beindicated by a change in the characteristics of the display to the useror the patient. For example, the trend arrow indicator may flash, changecolor, change shape, change size, change length or change width, amongothers. A further embodiment may include the trend arrow indicatorshowing no significant rate-of-change. Within the scope of the presentdisclosure, other user output configurations including audible and/orvibratory output are contemplated.

In one aspect, the uncertainty measure may be characterized a number ofways. One is the standard deviation of the monitored glucose levels overthe period in which the rate of change is estimated. Another is thecoefficient of variation (CV), which, as discussed above, is thestandard deviation of the monitored glucose trend divided by the rate ofchange value. A further characterization may include a probabilisticlikelihood estimate. Yet a further characterization is the output of astatistical filter or estimator such as a Kalman filter. The uncertaintycomparison may be based on one of these techniques or a combination oftwo or more of these techniques. Also, different uncertaintycharacteristics may be used for different rate-of-change results. Forinstance, in one embodiment, a CV formulation may be used for highglucose values and a standard deviation formulation may be used for lowglucose values.

FIG. 19 illustrates glucose trend determination in accordance with oneembodiment of the present disclosure. Referring to FIG. 19, a currentvalue associated with a monitored glucose level is received (1910). Oneor more prior values associated with the monitored glucose level(previously stored, for example) is retrieved (1920). With the currentand prior values associated with the monitored glucose level, a mostrecent calibration scale factor is applied to the current and priorvalues associated with the monitored glucose level (1930). Afterapplying the calibration scale factor to the current and prior values,the trend associated with the monitored glucose level is determined(1940).

In this manner, in one aspect, with the updated calibration of theglucose sensor including a newly determined sensitivity, buffered orstored values associated with the monitored glucose level may be updatedusing, for example, the updated calibration information, resulting, forexample, in revised or modified prior values associated with themonitored glucose level. As such, in one embodiment, stored or bufferedvalues associated with the monitored glucose level may be updated and,the updated values may be used to determine glucose trend information orrate of change of glucose level calculation. In this manner, accuracy ofthe glucose trend information may be improved by applying the mostrecent calibration parameters to previously detected and stored valuesassociated with the monitored glucose level, when, for example, thepreviously detected and stored values are used for further analysis,such as, glucose trend determination or rate of change of glucose levelcalculation.

FIG. 20 illustrates glucose trend determination in accordance withanother embodiment of the present disclosure. Referring to FIG. 20, acurrent value associated with a monitored glucose level is received(2010). One or more prior values associated with the monitored glucoselevel (previously stored, for example) is retrieved (2020). With thecurrent and prior values associated with the monitored glucose level, arate of change estimate of the monitored glucose level is determined(2030). Referring back to FIG. 20, an uncertainty parameter associatedwith the rate of change estimate is determined (2040).

In one aspect, an uncertainty parameter may be predetermined andprogrammed into the analyte monitoring system 100 (for example, in thereceiver unit 104/106). Alternatively, the uncertainty parameter may bedynamically configured to vary depending upon the number of dataavailable for determination of the glucose level rate of changedetermination, or upon other programmable parameters that may includeuser specified uncertainty parameters. Within the scope of the presentdisclosure, the uncertainty parameter may include the number ofacceptable missing or unavailable values when performing the monitoredglucose level rate of change estimation. Referring back to FIG. 20, whenit is determined that the uncertainty parameter is within an acceptablepredetermined tolerance range, the rate of change of the monitoredglucose level is determined and output to the user or the patient(2050).

In one embodiment, the uncertainty parameter may be associated with thetime spacing of the current and prior values, such that when the rate ofchange estimation requires a preset number of values, and no more than apredetermined number of values (optionally consecutively, or nonconsecutively) are unavailable, the rate of change estimation isperformed. In this manner, for example, when a large number of valuesassociated with the monitored glucose level (for example, 5 consecutiveone minute data−tolerance range) are unavailable, corrupt or otherwiseunusable for purposes of rate of change determination, the uncertaintyparameter is deemed to exceed the predetermined tolerance range, and therate of change calculation may not be performed, or may be postponed.

As discussed, the rate of change in glucose for a patient or a user maybe used by glucose monitoring devices to direct glucose trend indicatorsfor display to the patient or the user such that the patient or the usermay base treatment decisions not only on the current glucose levels butalso on the current direction or change in the glucose level. The rateof change estimate may also be used to project into the future if apredetermined glucose threshold (upper or lower range or limit) is notexceeded within a specific time period based on the current glucoselevel and rate of change information. Within the scope of the presentdisclosure, other projection approaches may be based on higher orderderivatives of the rate of change, and/or other statistical likelihoodformulations that can be contemplated for prediction of a future event.

One approach to determine the rate of change is to calculate thedifference between two glucose samples and dividing the result by thetime difference between the samples. Another approach may be to fit atime series of glucose readings to a function, such as a polynomial,using techniques such as the least squares techniques. The number ofsamples and the time period of the samples may impact the accuracy ofthe rate of change estimate in the form of a trade off between noisereduction properties and lag introduced.

Referring again to the Figures, in one aspect, the transmitter unit 102may be configured to perform one or more periodic or routine dataquality checks or verification before transmitting the data packet tothe receiver/monitor unit 104/106. For example, in one aspect, for eachdata transmission (e.g., every 60 seconds, or some other predeterminedtransmission time interval), the transmitter data quality flags in thedata packet are reset, and then it is determined whether any data fieldin the transmission data packet includes an error flag. If one errorflag is detected, then in one aspect, the entire data packet may beconsidered corrupt, and this determination is transmitted to thereceiver/monitor unit 104/106. Alternatively, the determination that theentire data packet is corrupt may be performed by the receiver/monitorunit 104/106. Accordingly, in one aspect, when at least one data qualitycheck fails in the transmitter data packet, the entire packet is deemedto be in error, and the associated monitored analyte level is discarded,and not further processed by the receiver/monitor unit 104/106.

In another aspect, the data quality check in the transmitter unit 102data packet may be performed so as to identify each error flag in thedata packet, and those identified error flag are transmitted to thereceiver/monitor unit 104/106 in addition to the associated monitoredanalyte level information. In this manner, in one aspect, if the errorflag is detected in the transmitter data packet which is not relevant tothe accuracy of the data associated with the monitored analyte level,the error indication is flagged and transmitted to the receiver/monitorunit 104/106 in addition to the data indicating the monitored analytelevel.

In one aspect, examples of error condition that may be detected orflagged in the transmitter unit 102 data packet include sensorconnection fault verification by, for example, determining, amongothers, whether the counter electrode voltage signal is within apredetermined range, resolution of the data associated with themonitored analyte level, transmitter unit temperature (ambient and/oron-skin temperature) out of range, and the like. As discussed above, thedata quality check in the transmitter unit 102 may be performedserially, such that detection of an error condition or an error flagrenders the entire data packet invalid or deemed corrupt. In this case,such data is reported as including error to the receiver/monitor unit104/106, but not used to process the associated monitored analyte level.In another aspect, all data quality fields in the data packet of thetransmitter unit 102 may be checked for error flags, and if there areerror flags detected, the indication of the detected error flags istransmitted with the data packet to the receiver/monitor unit 104/106for further processing.

In one embodiment, on the receiver/monitor unit 104/106 side, for eachperiodic data packet received (for example every 60 seconds or someother predetermined time interval), the receiver/monitor unit 104/106may be configured to receive the raw glucose data including any dataquality check flags from the transmitter unit 102, and to applytemperature compensation and/or calibration to the raw data to determinethe corresponding glucose data (with any data quality flags as may havebeen identified). The unfiltered, temperature compensated and/orcalibrated glucose data is stored along with any data quality flags in aFIFO buffer (including, for example, any invalid data identifier).Alternatively, a further data quality check may be performed on thetemperature compensated and calibrated glucose data to determine therate of change or variance of the measured glucose data. For example, inone embodiment, a high variance check or verification is performed on 30minutes of glucose data stored in the FIFO buffer. If it is determinedthat the rate of variance exceeds a predetermined threshold, then thedata packet in process may be deemed invalid. On the other hand, if therate of variance does not exceed the predetermined threshold, theresults including the glucose data and any associated validity or errorflags are stored in the FIFO buffer.

Thereafter, the data processing is performed on the stored data todetermine, for example, the respective glucose level estimation orcalculation. That is, the stored data in the FIFO buffer in oneembodiment is filtered to reduce unwanted variation in signalmeasurements due to noise or time delay, among others. In one aspect,when the rate of change or variance of glucose data stored in the FIFObuffer, for example, is within a predetermined limit, the glucosemeasurements are filtered over a 15 minute period. On the other hand, ifit is determined that the rate of change is greater than thepredetermined limit, a more responsive 2 minute filtering is performed.In one aspect, the filtering is performed for each 60 second glucosedata. In this manner, in one embodiment, a rate variance filter isprovided that may be configured to smooth out the variation in theglucose measurement when the glucose level is relatively stable, andfurther, that can respond quickly when the glucose level is changingrapidly. The rate variance filter may be implemented in firmware as anFIR filter which is stable and easy to implement in integer-basedfirmware, for example, implemented in fixed point math processor.

In one embodiment, for each 60 second glucose data received, twofiltered values and two additional parameters are determined. That is,using an FIR filter, for example, a weighted average for a 15 minutefiltered average glucose value and a 2 minute average filtered glucosevalue are determined. In addition, a rate of change based on 15 minutesof data as well as a standard deviation associated with the rateestimate is determined. To determine the final filtered glucose valuefor output and/or display to the user, a weighted average of the twodetermined filtered glucose values is determined, where when the rate ofchange of the glucose values is high, then weighting is configured totend towards the 2 minute filtered value, while when the rate of changeof the glucose value is low the weighting tends towards the 15 minutefiltered value. In this manner, when the rate of change is high, the 2minute filtered value is weighted more heavily (as the 15 minutefiltered average value potentially introduces lag, which at higher ratesof change, likely results in large error).

Referring back, during the calibration routine, in one embodiment, whenthe discrete blood glucose value is received for purposes of calibrationof the glucose data from the sensor 101 (FIG. 1), the processing unit ofthe receiver/monitor unit 104/106 is configured to retrieve from theFIFO buffer two of the last five valid transmitter data packets that donot include any data quality flags associated with the respective datapackets. In this manner, in one aspect, the calibration validation checkmay be performed when the blood glucose value is provided to thereceiver/monitor unit 104/106 determined using, for example, a bloodglucose meter. In the event that two valid data packets from the lastfive data packets cannot be determined, the receiver/monitor unit104/106 is configured to alarm or notify the user, and the calibrationroutine is terminated.

On the other hand, if the calibration validation check is successful,the sensitivity associated with the sensor 101 (FIG. 1) is determined,and its range verified. In one aspect, if the sensitivity range checkfails, again, the receiver/monitor unit 104/106 may be configured toalarm or otherwise notify the user and terminate the calibrationroutine. Otherwise, the determined sensitivity is used for subsequentglucose data measurement and processing (until a subsequent calibrationis performed).

Referring back to the Figures, in one aspect, determination of optimalsensitivity evaluates one or more potential error sources or conditionspresent in blood glucose value for calibration and the potentialsensitivity drift. Accordingly, using a weighted average of the currentsensitivity determined for calibration and previously determinedsensitivity, the sensitivity accuracy may be optimized. For example, inone embodiment, a weighted average of the two most recent sensitivitiesdetermined used for calibration may be used to determine a compositesensitivity determination to improve accuracy and reduce calibrationerrors. In this aspect, earlier blood glucose values used forcalibration are discarded to accommodate for sensitivity drift. In oneembodiment, the number of blood glucose values used for determining theweighted average, and also, the weighting itself may be varied using oneor more approaches including, for example, a time based technique.

For example, for each sensor calibration routine, the sensitivityderived from the current blood glucose value from the current bloodglucose test and the stored sensitivity value associated with the mostrecent prior stored blood glucose value may be used to determine aweighted average value that is optimized for accuracy. Within the scopeof the present disclosure, as discussed above, the weighting routine maybe time based such that if the earlier stored blood glucose value usedfor prior calibration is greater than a predetermined number of hours,then the weighting value assigned to the earlier stored blood glucosemay be less heavy, and a more significant weighting value may be givento the current blood glucose value to determine the compositesensitivity value.

In one embodiment, a lookup table may be provided for determining thecomposite sensitivity determination based on a variable weightingaverage which provides a non-linear correction to reduce errors andimprove accuracy of the sensor sensitivity.

The determined composite sensitivity in one embodiment may be used toconvert the sensor ADC counts to the corresponding calibrated glucosevalue. In one aspect, the composite sensitivity determined may be usedto minimize outlier calibrations and unstable sensitivity during, forexample, the initial use periods. That is, during the data validationroutines, an outlier check may be performed to determine whether thesensitivity associated with each successive calibration is within apredetermined threshold or range.

For example, the sensor 101 (FIG. 1) may require a predetermined numberof baseline calibrations during its use. For a five day operationallifetime of a sensor, four calibrations may be required at differenttimes during the five day period. Moreover, during this time period,additional stability related calibrations may be required if the sensorsensitivity is determined to be unstable after the second baselinecalibration is performed, for example, at the 12^(th) hour (or othersuitable time frame) of the sensor usage after the initial calibrationwithin the first 10 hours of sensor deployment.

In one aspect, during the outlier check routine, it is determinedwhether the sensitivity variance between two successive calibrations iswithin a predetermined acceptable range. If it is determined that thevariance is within the predetermined range, then the outlier check isconfirmed, and a new composite sensitivity value is determined based ona weighted average of the two sensitivity values. As discussed above,the weighted average may include a time based function or any othersuitable discrete weighting parameters.

If on the other hand, the variance between the two sensitivities isdetermined to be outside of the predetermined acceptable range, then thesecond (more recent) sensitivity value is considered to be an outlier(for example, due to ESA, change in sensitivity or due to bad orerroneous blood glucose value), and the user is prompted to performanother fingerstick testing to enter a new blood glucose value (forexample, using a blood glucose meter). If the second current sensitivityassociated with the new blood glucose value is determined to be withinthe predetermined acceptable range from the prior sensitivity, then theearlier current sensitivity value is discarded, and the compositesensitivity is determined based on applying a weighting function orparameter on the prior sensitivity value, and the second currentsensitivity value (discarding the first current sensitivity value whichis outside the predetermined acceptable range and considered to be anoutlier).

On the other hand, when the second current sensitivity value isdetermined to be within the predetermined acceptable range of the firstcurrent sensitivity value, but not within the predetermined acceptablerange of the prior sensitivity value (of the two successive calibrationsdescribed above), then it is determined in one embodiment that asensitivity shift, rather than an outlier, has occurred or is detectedfrom the first current sensitivity value to the second currentsensitivity value. Accordingly, the composite sensitivity may bedetermined based, in this case, on the first and second currentsensitivity values (and discarding the prior sensitivity).

If, for example, the second current sensitivity value is determined tobe outside the predetermined range of both of the two successivesensitivities described above, then the user in one embodiment isprompted to perform yet another blood glucose test to input anothercurrent blood glucose value, and the routine described above isrepeated.

Furthermore, in accordance with another aspect, the determination of thesensitivity variance between two successive calibrations is within apredetermined acceptable range may be performed prior to the outliercheck routine.

Referring to the Figures, during the period of use, as discussed above,the sensor 101 (FIG. 1) is periodically calibrated at predetermined timeintervals. In one aspect, after the second baseline calibration (forexample, at 12^(th) hour of sensor 101 transcutaneously positioned influid contact with the user's analyte), sensor sensitivity stabilityverifications may be performed to determine whether, for example,additional stability calibrations may be necessary before the thirdbaseline calibration is due. In one aspect, the sensitivity stabilityverification may be performed after the outlier checks as describedabove is performed, and a new composite sensitivity is determined, andprior to the third scheduled baseline calibration at the 24^(th) hour(or at another suitable scheduled time period).

That is, the sensor sensitivity may be attenuated (e.g., ESA) early inthe life of the positioned sensor 101 (FIG. 1), and if not sufficientlydissipated by the time of the first baseline calibration, for example,at the 10^(th) hour (or later), and even by the time of the secondcalibration at the 12^(th) hour. As such, in one aspect, a relativedifference between the two sensitivities associated with the twocalibrations is determined. If the determined relative difference iswithin a predefined threshold or range (for example, approximately 26%variation), then it is determined that the sufficient stability pointhas been reached. On the other hand, if the relative differencedetermined is beyond the predefined threshold, then the user is promptedto perform additional calibrations at a timed interval (for example, ateach subsequent 2 hour period) to determine the relative difference inthe sensitivity and compared to the predefined range. This may berepeated for each two hour interval, for example, until acceptablestability point has been reached, or alternatively, until the timeperiod for the third baseline calibration is reached, for example, atthe 24^(th) hour of sensor 101 (FIG. 1) use.

In this manner, in one aspect, the stability verification may bemonitored as the sensitivity attenuation is dissipating over a giventime period. While the description above is provided with particulartime periods for baseline calibrations and additional calibrationprompts for stability checks, for example, within the scope of thepresent disclosure, other time periods or calibration schedule includingstability verifications may be used. In addition, other suitablepredefined threshold or range of the relative sensitivity difference todetermine acceptable attenuation dissipation other than approximately26% may be used. Moreover, as discussed above, the predeterminedcalibration schedule for each sensor 101 (FIG. 1) may be modified fromthe example provided above, based on, for example, the system designand/or sensor 101 (FIG. 1) configuration.

Additionally, in one aspect, the user may be prompted to perform thevarious scheduled calibrations based on the calibration scheduleprovided. In the case where the scheduled calibration is not performed,in one embodiment, the glucose value determination for user display oroutput (on the receiver/monitor unit 104/106, for example) based on thereceived sensor data may be disabled after a predetermined time periodhas lapsed. Further, the glucose value determination may be configuredto resume when the prompted calibration is successfully completed.

In a further aspect, the scheduled calibration timing may be relative tothe prior calibration time periods, starting with the initial sensorpositioning. That is, after the initial transcutaneous positioning ofthe sensor 101 (FIG. 1) and the scheduled time period has elapsed toallow the sensor 101 to reach a certain stability point, the user may beprompted to perform the first baseline calibration as described above(for example, at the 10^(th) hour since the initial sensor placement).Thereafter, in the case when the user waits until the 11^(th) hour toperform the initial baseline calibration, the second scheduledcalibration at the 12^(th) hour, for example, may be performed at the13^(th) hour, so that the two hour spacing between the two calibrationsare maintained, and the second calibration timing is based on the timingof the first successful baseline calibration performed. In an alternateembodiment, each scheduled calibration time period may be based on thetiming of the initial sensor positioning. That is, rather thandetermining the appropriate subsequent calibration time periods based onthe prior calibration performed, the timing of the scheduled calibrationtime periods may be made to be absolute and based from the time of theinitial sensor placement.

Furthermore, in one aspect, when the scheduled calibration is notperformed at the scheduled time periods, the glucose values maynevertheless be determined based on the sensor data for display to theuser for a limited time period (for example, for no more than two hoursfrom when the scheduled calibration time period is reached). In thismanner, a calibration time window may be established or provided to theuser with flexibility in performing the scheduled calibration and duringwhich the glucose values are determined for output display to the user,for example. In one aspect, if within the calibration time window, thescheduled calibrations are not performed, the glucose values may bedeemed in error, and thus not provided to the user or determined untilthe calibration is performed.

For example, after the initial successful baseline calibration at the10^(th) hour, for example, or at any other suitable scheduled initialbaseline calibration time, glucose values are displayed or output to theuser and stored in a memory. Thereafter, at the next scheduledcalibration time period (for example, at the 12^(th) hour), the user maybe prompted to perform the second calibration. If the user does notperform the second calibration, a grace period of two hours, forexample, is provided during which valid glucose values are provided tothe user (for example, on the display unit of the receiver/monitor unit104/106) based on the prior calibration parameters (for example, theinitial baseline calibration performed at the 10^(th) hour). However, ifthe second calibration is still not performed after the grace period, inone aspect, no additional glucose values are provided to user, and untilthe scheduled calibration is performed.

In still another aspect, the user may supplement the scheduledcalibrations, and perform manual calibration based on the informationthat the user has received. For example, in the case that the userdetermines that the calibration performed and determined to besuccessful by the receiver/monitor unit 104/106, for example, is notsufficiently accurate, rather than replacing the sensor, the user mayrecalibrate the sensor even if the scheduled calibration time has notbeen reached. For example, based on a blood glucose test result, if thedetermined blood glucose level is not close to or within an acceptablerange as compared to the sensor data, the user may determine thatadditional calibration may be needed.

Indeed, as the sensitivity value of a given sensor tends to stabilizeover time, a manual user forced calibration later in the sensor's lifemay provide improved accuracy in the determined glucose values, ascompared to the values based on calibrations performed in accordancewith the prescribed or predetermined calibration schedule. Accordingly,in one aspect, additional manual calibrations may be performed inaddition to the calibrations based on the predetermined calibrationschedule.

In a further aspect, user notification functions may be programmed inthe receiver/monitor unit 104/106, or in the transmitter unit 102(FIG. 1) to notify the user of initial conditions associated with thesensor 101 (FIG. 1) performance or integrity. That is, alarms or alerts,visual, auditory, and/or vibratory may be configured to be triggeredwhen conditions related to the performance of the sensor is detected.For example, during the initial one hour period (or some other suitabletime period) from the sensor insertion, in the case where data qualityflags/conditions (described above) are detected, or in the case wherelow or no signal from the sensor is detected from a given period oftime, an associated alarm or notification may be initiated or triggeredto notify the user to verify the sensor position, the sensor contactswith the transmitter unit 102 (FIG. 1), or alternatively, to replace thesensor with a new sensor. In this manner, rather than waiting a longerperiod until the acceptable sensor stability point has been reached, theuser may be provided at an early stage during the sensor usage that thepositioned sensor may be defective or has failed.

In addition, other detected conditions related to the performance of thesensor, calibration, and detected errors associated with the glucosevalue determination may be provided to the user using one or more alarmor alert features. For example, when the scheduled calibration has beentimely performed, and the grace period as described above has expired,in one embodiment, the glucose value is not processed for display oroutput to the user anymore. In this case, an alarm or alert notifyingthe user that the glucose value cannot be calculated is provided so thatthe user may timely take corrective actions such as performing thescheduled calibration. In addition, when other parameters that aremonitored such as the temperature, sensor data, and other variables thatare used to determine the glucose value, include error or otherwise isdeemed to be corrupt, the user may be notified that the associatedglucose value cannot be determined, so that the user may take correctiveactions such as, for example, replacing the sensor, verifying thecontacts between the sensor and the transmitter unit, and the like.

In this manner, in one embodiment, there is provided an alarm ornotification function that detects or monitors one or more conditionsassociated with the glucose value determination, and notifies the userof the same when such condition is detected. Since the alarms ornotifications associated with the glucose levels (such as, for example,alarms associated with potential hyperglycemic, hypoglycemic, orprogrammed trend or rate of change glucose level conditions) will beinactive if the underlying glucose values cannot be determined, byproviding a timely notification or alarm to the user that the glucosevalue cannot be determined, the user can determine or beprompted/notified that these alarms associated with glucose levels areinactive.

In one aspect of the present disclosure, glucose trend information maybe determined and provided to the user, for example, on thereceiver/monitor unit 104/106. For example, trend information in oneaspect is based on the prior monitored glucose levels. When calibrationis performed, the scaling used to determine the glucose levels maychange. If the scaling for the prior glucose data (for example, oneminute prior) is not changed, then in one aspect, the trenddetermination may be deemed more error prone. Accordingly, in oneaspect, to determine accurate and improved trend determination, theglucose level determination is performed retrospectively for a 15 minutetime interval based on the current glucose data when each successiveglucose level is determined.

That is, in one aspect, with each minute determination of the real timeglucose level, to determine the associated glucose trend information,the stored past 15 minute data associated with the determined glucoselevel is retrieved, including the current glucose level. In this manner,the buffered prior glucose levels may be updated with new calibration toimprove accuracy of the glucose trend information.

In one aspect, the glucose trend information is determined based on thepast 15 minutes (or some other predetermined time interval) of glucosedata including, for example, the current calibration parameter such ascurrent sensitivity. Thereafter, when the next glucose data is received(at the next minute or based on some other timed interval), a newsensitivity is determined based on the new data point associated withthe new glucose data. Also, the trend information may be determinedbased on the new glucose data and the past 14 minutes of glucose data(to total 15 minutes of glucose data). It is to be noted that while thetrend information is determined based on 15 minutes of data as describedabove, within the scope of the present disclosure, other time intervalsmay be used to determine the trend information, including, for example,30 minutes of glucose data, 10 minutes of glucose data, 20 minutes ofglucose data, or any other appropriate time intervals to attain anaccurate estimation of the glucose trend information.

In this manner, in one aspect of the present disclosure, the trendinformation for the historical glucose information may be updated basedon each new glucose data received, retrospectively, based on the new orcurrent glucose level information, and the prior 14 glucose data points(or other suitable number of past glucose level information). In anotheraspect, the trend information may be updated based on a select number ofrecent glucose level information such that, it is updated periodicallybased on a predetermined number of determined glucose level informationfor display or output to the user.

In still another aspect, in wireless communication systems such as thedata monitoring and management system 100 (FIG. 10), the devices orcomponents intended for wireless communication may periodically be outof communication range. For example, the receiver/monitor unit 104/106may be placed out of the RF communication range of the transmitter unit102 (FIG. 1). In such cases, the transmitted data packet from thetransmitter unit 102 may not be received by the receiver/monitor unit104/106, or due to the weak signaling between the devices, the receiveddata may be invalid or corrupt. In such cases, while there may bemissing data points associated with the periodically monitored glucoselevels, the trend information may be nevertheless determined, as thetrend information is determined based on a predetermined number of pastor prior glucose data points (for example, the past 15 minutes ofglucose data).

That is, in one aspect, even if there are a certain number of glucosedata points within the 15 minute time frame that may be either notreceived by the receiver/monitor unit 104/106, or alternatively becorrupt or otherwise invalid due to, for example, weakness in thecommunication link, the trend information may be determined. Forexample, given the 15 minutes of glucose data, if three or less nonconsecutive data points are not received or otherwise corrupt, thereceiver/monitor unit 104/106 may determine the glucose trendinformation based on the prior 12 glucose data points that are receivedand considered to be accurate. As such, the features or aspects of theanalyte monitoring system which are associated with the determined trendinformation may continue to function or operate as programmed.

That is, the projected alarms or alerts programmed into thereceiver/monitor unit 104/106, or any other alarm conditions associatedwith the detection of impending hyperglycemia, impending hypoglycemia,hyperglycemic condition or hypoglycemic condition (or any other alarm ornotification conditions) may continue to operate as programmed even whenthere are a predetermined number or less of glucose data points.However, if and when the number of missing glucose data points exceedthe tolerance threshold so as to accurately estimate or determine, forexample, the glucose trend information, or any other associated alarmconditions, the display or output of the associated glucose trendinformation or the alarm conditions may be disabled.

For example, in one aspect, the glucose trend information and the rateof change of the glucose level (which is used to determine the trendinformation) may be based on 15 minute data (or data based on any othersuitable time period) of the monitored glucose levels, where apredetermined number of missing data points within the 15 minutes may betolerated. Moreover, using least squares approach, the rate of change ofthe monitored glucose level may be determined to estimate the trend,where the monitored glucose data is not evenly spaced in time. In thisapproach, the least squares approach may provide an uncertainty measureof the rate of change of the monitored glucose level. The uncertainlymeasure, in turn, may be partially dependent upon the number of datapoints available.

Indeed, using the approaches described above, the trend information orthe rate of change of the glucose level may be estimated or determinedwithout the need to determine which data point or glucose level istolerable, and which data point is not tolerable. For example, in oneembodiment, the glucose data for each minute including the missing datais retrieved for a predetermined time period (for example, 15 minutetime period). Thereafter, least squares technique is applied to the 15minute data points. Based on the least squares (or any otherappropriate) technique, the uncertainly or a probability of potentialvariance or error of the rate of glucose level change is determined. Forexample, the rate of change may be determined to be approximately 1.5mg/dL/minute +/−0.1 mg/dL/minute. In such a case, the 0.1 mg/dL/minutemay represent the uncertainly information discussed above, and may behigher or lower depending upon the number of data points in the 15minutes of data that are missing or corrupt.

In this manner, in one aspect, the glucose trend information and/or therate of change of monitored glucose level may be determined based on apredefined number of past monitored glucose level data points, even whena subset of the predefined number of past monitored glucose level datapoints are missing or otherwise determined to be corrupt. On the otherhand, when the number of past glucose level data points based on whichthe glucose trend information is determined, exceeds the tolerance oracceptance level, for example, the display or output of the glucosetrend information may be disabled. Additionally, in a further aspect, ifit is determined that the underlying data points associated with themonitored glucose level based on which the trend information isdetermined, includes uncertainly or error factor that exceeds thetolerance level (for example, when there are more than a predeterminednumber of data points which deviate from a predefined level), thereceiver/monitor unit 104/106, for example, may be configured to disableor disallow the display or output of the glucose trend information.

For example, when the 15 minute glucose data including the currentglucose level as well as the past 14 minutes of glucose level data is tobe displayed or output to the user, and the determined rate variance ofthe 15 data points exceeds a preset threshold level (for example, 3.0),the glucose trend information display function may be disabled. In oneaspect, the variance may be determined based on the square function ofthe standard deviation of the 15 data points. In one aspect, thisapproach may be performed substantially on a real time basis for eachminute glucose data. Accordingly, as discussed above, the glucose trendinformation may be output or displayed substantially in real time, andbased on each new glucose data point received from thesensor/transmitter unit.

Additionally, when it is determined that the 15 data points (or anyother suitable number of data points for determining glucose trendinformation, for example), deviate beyond a predetermined tolerancerange, in one aspect, the 15 minute data may be deemed error prone orinaccurate. In this case, rather than outputting or displaying glucosetrend information that may be erroneous, the receiver/monitor unit104/106 may be configured to display the output or display functionrelated to the output or display of the determined glucose trendinformation. The same may apply to the output or display of projectedalarms whose estimates may be based in part, on the determined trendinformation. Accordingly, in one aspect, there may be instances when theprojected alarm feature may be temporarily disabled where the underlyingmonitored glucose data points are considered to include more thanacceptable levels of uncertainly or error.

In a further aspect, it is desired to determine an estimate of sensorsensitivity, and/or a range of acceptable or reasonable sensitivity. Forexample, during determination or verification of the glucose rate ofchange prior to calibration, the estimated sensor sensitivityinformation is necessary, for example, to determine whether the rate ofchange is within or below an acceptable threshold level, and/or further,within a desired range. Moreover, when determining whether the sensorsensitivity is within an acceptable or reasonable level, it may benecessary to ascertain a range of reasonable or acceptablesensitivity—for example, a verification range for the sensitivity valuefor a given sensor or batch of sensors.

Accordingly, in one aspect, during sensor manufacturing process, apredetermined number of sensor samples (for example, 16 samples) may beevaluated from each manufacturing lot of sensors (which may include, forexample, approximately 500 sensors) and the nominal sensitivity for eachlot (based, for example, on a mean calculation) may be determined. Forexample, during the manufacturing process, the predetermined number ofsensors (for example, the 16 sensors) is sampled, and the sensitivity ofeach sampled sensor is measured in vitro. Thereafter, a mean sensitivitymay be determined as an average value of the 16 sampled sensor'smeasured sensitivity, and thereafter, the corresponding sensor code isdetermined where the determined mean sensitivity falls within thepreassigned sensitivity range. Based on the determined sensor code, thesensor packaging is labeled with the sensor code.

For example, each sensor code value (e.g., 105, 106, 107 or any suitablepredetermined number or code) may be preassigned a sensitivity range(For example, code 105: S1-S2, code 106: S2-S3, and code 107: S3-S4),where each sensitivity range (e.g., S1-S2, or S2-S3, or S3-S4) isapproximately over a 10 percent increment (for example, S1 isapproximately 90% of S2). Also, each sensor code (e.g., 105, 106, 107etc) is assigned a nominal sensitivity value (Sn) that is within therespective preassigned sensitivity range.

Referring back, when the user inserts the sensor or positions the sensortranscutaneously in place, the receiver/monitor unit 104/106 in oneembodiment prompts the user to enter the associated sensor code. Whenthe user enters the sensor code (as derived from the sensor packinglabel discussed above), the receiver/monitor unit 104/106 is configuredto retrieve or look up the nominal sensitivity associated with the userinput sensor code (and the nominal sensitivity which falls within thepreassigned sensitivity range associated with that sensor code, asdescribed above). Thereafter, the receiver/monitor unit 104/106 may beconfigured to use the sensor code in performing associated routines suchas glucose rate of change verification, data quality checks discussedabove, and/or sensor sensitivity range acceptability or confirmation.

In a further aspect, the sensor codes may be associated with acoefficient of variation of the predetermined number of sampled sensorsdiscussed above in addition to using the mean value determined asdiscussed above. In one embodiment, the coefficient of variation may bedetermined from the predetermined number of sampled sensors during themanufacturing process. In addition, the mean response time of thesampled sensors may be used by separately measuring the predeterminednumber of sampled sensors which may be used for lag correctionadjustments and the like.

In this manner, in one aspect, the manufacturing process controldescribed above ensures that the coefficient of variation of the sampledsensors is within a threshold value. That is, the value of the nominalsensitivity is used to determine a sensor code, selected or looked upfrom a predetermined table, and that is assigned to the sensors from therespective sensor lot in manufacturing. The user then enters the sensorcode into the receiver/monitor unit that uses the sensor code todetermine the glucose rate of change for purposes of data qualitychecking, for example, and also to determine validity or reasonablenessof the sensitivity that is determined.

In one embodiment, a method may comprise sampling a predetermined numberof in vivo analyte sensors, determining a sensitivity value for each ofthe sampled predetermined number of analyte sensors, and determining amean sensitivity based on the sensitivity value of the predeterminednumber of analyte sensors.

The predetermined number of analyte sensors may be approximately 100 orless.

The sensitivity value may be determined in vitro.

The in vitro determination of the sensitivity value may includemeasuring the sensitivity value for each analyte sensor.

Measuring the sensitivity value for each analyte sensor may be performedduring sensor manufacturing.

One aspect may include determining a sensor code associated with apredetermined sensitivity range.

The mean sensitivity may be within the predetermined sensitivity range.

The sensor code may be used to calibrate the analyte sensors.

The sensor code may be stored in an analyte monitoring device.

One aspect may include determining a deviation of the sensitivity valueto a predetermined level.

One aspect may include when the determined deviation exceeds a tolerancethreshold level, rejecting the predetermined number of analyte sensorsduring manufacturing.

In one embodiment a method may comprise, receiving a sensor code,retrieving a sensitivity associated with the sensor code correspondingto an analyte sensor, and performing data processing based at least inpart on the sensor code.

The sensor code may be associated with a predetermined sensitivityrange.

The sensitivity may be within the predetermined sensitivity range.

One aspect may include storing the sensor code.

One aspect may include performing data processing which may include oneor more of a glucose rate verification routine, a data integrityverification routine, or a predetermined sensitivity range validityverification.

In one embodiment an apparatus may comprise a data processing unitconfigured to receive an analyte sensor code, retrieve a sensitivityassociated with the sensor code corresponding to an analyte sensor, andperform data processing based at least in part on the sensor code.

The sensor code may be associated with a predetermined sensitivityrange.

The sensitivity may be within the predetermined sensitivity range.

The data processing unit may be configured to perform one or more of aglucose rate verification routine, a data integrity verificationroutine, or a predetermined sensitivity range validity verification.

One aspect may include a data storage unit for storing one or more ofthe sensor code or the sensitivity.

The data processing unit may be configured to determine a coefficient ofvariation based on a sampled predetermined number of analyte sensors.

The sampled predetermined number of analyte sensors may include a subsetof each sensor lot during manufacturing.

Various other modifications and alterations in the structure and methodof operation of this invention will be apparent to those skilled in theart without departing from the scope and spirit of the invention.Although the invention has been described in connection with specificpreferred embodiments, it should be understood that the invention asclaimed should not be unduly limited to such specific embodiments. It isintended that the following claims define the scope of the presentdisclosure and that structures and methods within the scope of theseclaims and their equivalents be covered thereby.

What is claimed is:
 1. A method, executed using one or more processors,of manufacturing analyte sensors, the method comprising: determining asensitivity value for each of a predetermined number of analyte sensors;determining a sensitivity variation for the predetermined number ofanalyte sensors; determining a mean sensitivity based on the sensitivityvalue determined for each of the predetermined number of analyte sensorswhen it is determined that a determined sensitivity variation does notexceed a tolerance threshold level; and associating a sensor code withan analyte sensor batch associated with the predetermined number ofanalyte sensors when the mean sensitivity is within a predeterminedsensitivity range.